Epidemiology
Prevalence of afibrinogenemia is estimated at 1/1,000,000. Hypo- and dysfibrinogenemia are more frequent. Both sexes are equally affected. Fibrinogen deficiency can be discovered at any age but afibrinogenemia usually manifests early in childhood, often in the neonatal period.

Clinical description
Common manifestations of afibrinogenemia include umbilical cord bleeding, epistaxis, hemarthrosis, gastrointestinal bleeding, menorrhagia, traumatic and surgical bleeding and, rarely, intracranial hemorrhage. Recurrent spontaneous abortions may occur in women affected with afibrinogenemia. Hypofibrinogenemia is characterized by fewer and milder bleeding episodes following trauma or surgery. Most of patients with dysfibrinogenemia are asymptomatic (60%). The others may have bleeding symptoms (28%) or even thrombosis (20%).

Etiology
Congenital deficiencies of fibrinogen are caused by mutations in the FGA, FGB, or FGG genes. Afibrinogenemia is autosomal recessive; hypofibrinogenemia and dysfibrinogenemia are mainly autosomal dominant.

Diagnostic methods
Diagnosis is based on prolonged activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin and reptilase times and on fibrinogen levels measured by functional (Clauss) and immunological assays.

Differential diagnosis
Differential diagnoses include the other congenital clotting factor deficiencies (Factors II, V, VII, X, XI, VIII, IX and XIII; see these terms) and acquired fibrinogen deficiency (consumptive coagulopathy, hepatic failure). In case of thrombosis, differential diagnosis also includes congenital or acquired thrombophilia (antithrombin deficiency, protein C or S deficiency, Factor V Leiden mutation, lupus anticoagulant (see these terms) and FII Leiden mutation).

Antenatal diagnosis
Antenatal diagnosis of afibrinogenemia is possible if the causal mutations have already been identified in the family.

The information is taken from the website Orpha.net